Normal Development - Milk
|Embryology - 15 Nov 2018 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Mammary Glands Pregnancy
- 4 Milk Composition
- 5 Human Milk
- 6 Immunity
- 7 Milk Production
- 8 Environmental Contaminants
- 9 Abnormalities
- 10 References
- 11 External Links
- 12 Glossary Links
Breast milk makes us mammals! This current page discusses some issues related to milk and neonatal nutrition, it is not a guide to breastfeeding, which is covered by many other resources. The composition of milk can vary over time, with colostrum the initial yellowish, sticky breast milk produced at the end of pregnancy.
The review article (abstract shown below) by Goldman in 2000 may provide a way of thinking about gastrointestinal tract and human milk.
There are other resource pages that cover the topic of breast development (More? mammary gland). Milk also has important role in gastrointestinal tract postnatal development (More? gastrointestinal tract)
|Postnatal Links: birth | neonatal | neonatal diagnosis | milk | Nutrition | growth charts | Disease School Exclusion | vaccination | puberty | genital|
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Amy G Bryant, Anne Drapkin Lyerly, Stephanie DeVane-Johnson, Christine E Kistler, Alison M Stuebe Hormonal contraception, breastfeeding, and bedside advocacy: the case for patient-centered care. Contraception: 2018; PubMed 30423320
Evelyn Jantscher-Krenn, Johanna Aigner, Birgit Reiter, Harald Köfeler, Bence Csapo, Gernot Desoye, Lars Bode, Mireille N M Van Poppel Evidence of Human Milk Oligosaccharides in maternal circulation already during pregnancy - a pilot study. Am. J. Physiol. Endocrinol. Metab.: 2018; PubMed 30422706
Xiao Ru, Chuang-Chuang Zhang, Ya-Hong Yuan, Tian-Li Yue, Chun-Feng Guo Bile salt hydrolase activity is present in nonintestinal lactic acid bacteria at an intermediate level. Appl. Microbiol. Biotechnol.: 2018; PubMed 30421106
Melvin C L Gay, Petya T Koleva, Carolyn M Slupsky, Elloise du Toit, Merete Eggesbo, Christine C Johnson, Ganesa Wegienka, Naoki Shimojo, Dianne E Campbell, Susan L Prescott, Daniel Munblit, Donna T Geddes, Anita L Kozyrskyj, InVIVO LactoActive Study Investigators Worldwide Variation in Human Milk Metabolome: Indicators of Breast Physiology and Maternal Lifestyle? Nutrients: 2018, 10(9); PubMed 30420587
Virginia Meikle, Ann-Kristin Mossberg, Avishek Mitra, Anders P Hakansson, Michael Niederweis ##Title## Antimicrob. Agents Chemother.: 2018; PubMed 30420480
Mammary Glands Pregnancy
During pregnancy raised estrogens and progesterone stimulate gland development, secretory alveolar structures form and differentiate, leading to milk production in late pregnancy and milk secretion during lactation. Breasts are hemispherical in shape due to fat deposition. After birth, neonatal lactation supports further growth/development.
Most mammals produce milk containing similar components which may occur at different concentrations. Composition of the maternal diet can affect the concentration of some of these components. In addition, some materal environmental components can also appear in the milk.
Typical secreted milk contains:
- Carbohydrate: lactose, glucose, galactose, and oligosaccharides
- Fats: triglycerides and fatty acids (omega-3 polyunsaturated fatty acids, such as docosahexanoic acid)
- Proteins: caseins, alpha-lactalbumin, immunoglobulins, albumin, lactoferrin, nonprotein nitrogen, enzymes, hormones, growth factors, and nucleotides
- Trace elements: selenium and iodine
- Vitamins: A, B1 (thiamin), B2 (riboflavin), B5 (pantothenic acid), B6 (pyridoxine), B12 (cobalamin), D, and E
A bioactive protein in mammal milk with various neonatal actions, such as anti-infective, immunological, and gastrointestinal.
- "Human milk contains agents that affect the growth, development and functions of the epithelium, immune system or nervous system of the gastrointestinal tract. Some human and animal studies indicate that human milk affects the growth of intestinal villi, the development of intestinal disaccharidases, the permeability of the gastrointestinal tract and resistance to certain inflammatory/immune-mediated diseases. Moreover, one cytokine in human milk, interleukin (IL)-10, protects infant mice genetically deficient in IL-10 against an enterocolitis that resembles necrotizing enterocolitis (NEC) in human premature infants.
There are seven overlapping evolutionary strategies regarding the relationships between the functions of the mammary gland and the infant’s gastrointestinal tract as follows:
- certain immunologic agents in human milk compensate directly for developmental delays in those same agents in the recipient infant
- other agents in human milk do not compensate directly for developmental delays in the production of those same agents, but nevertheless protect the recipient
- agents in human milk enhance functions that are poorly expressed in the recipient
- agents in human milk change the physiologic state of the intestines from one adapted to intrauterine life to one suited to extrauterine life
- some agents in human milk prevent inflammation in the recipient’s gastrointestinal tract
- survival of human milk agents in the gastrointestinal tract is enhanced because of delayed production of pancreatic proteases and gastric acid by newborn infants, antiproteases and inhibitors of gastric acid production in human milk, inherent resistance of some human milk agents to proteolysis, and protective binding of other factors in human milk
- growth factors in human milk aid in establishing a commensal enteric microflora"
(Text from: Goldman AS. Modulation of the gastrointestinal tract of infants by human milk. Interfaces and interactions. An evolutionary perspective.)
In addition to maternal antibodies, milk contains maternal lymphocytes (antibody-producing B cells. T cells, and natural killer cells). In a mouse model, maternal cytotoxic T cells within milk have been shown to transfer into to the neonatal intestinal Peyer's patches.Cite error: Invalid
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The neonatal immune system (innate and adaptive) is immature and still developing, and there is now good evidence that milk contributes to the developmental process, see review.
Development of the breasts and milk production is mainly regulated by the anterior pituitary hormone prolactin (PRL). The release of prolactin is regulated by the hypothalamus prolactin-releasing hormone (PRLH, prolactin-releasing peptide, PRRP)
Prolactin hormone other roles include:
- regulating follicle stimulating hormone (FSH) effect on the ovary.
- increased maternal myelination processes during pregnancy.
Prolactin-releasing hormone (PRLH, prolactin-releasing peptide, PRRP) is an 87 amino acid peptide hypothalamus hormone which regulates anterior pituitary release of prolactin.
Prolactin signaling Pathway
In the mammary gland:
- Prolactin binds to its receptor (PRLR) and causes them to dimerize.
- Receptor-associated tyrosine kinase Jak2 phosphorylates: the prolactin receptor and Stat5a and Stat5b (signal transducers and activators of transcription).
- Activated Stat5a and -5b are transported into the nucleus
- They specifically bind DNA of target genes (the GAS sequence, TTCNNNGAA).
- Induce transcription that promote: proliferation, differentiation, and lactogenesis.
Environmental components (contaminants) that appear in the milk may depend on the origin (maternal, cow) or the water quality used in formula preparation.
- Lead levels in human milk and children's health risk: a systematic review 
- Relationships of lead in breast milk to lead in blood, urine, and diet of the infant and mother "The levels of lead in breast milk are thus similar to those in plasma. Breast-fed infants are only at risk if the mother is exposed to high concentrations of contaminants either from endogenous sources such as the skeleton or exogenous sources."
- Effect of breast milk lead on infant blood lead levels at 1 month of age
- polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), chlordane compounds (CHLs), hexachlorobenzene (HCB)
Galactorrhoea is the clinical term for inappropriate production of milk that is often associated with anterior pituitary tumours producing excess prolactin. This condition can occur in both females and males.
In galactosaemia babies cannot process galactose, a component of lactose. Incidence is about 1 in 40,000 births (about 1-3 cases per year). Life-threatening liver failure and infections can occur. A galactose-free diet instituted in the first postnatal week can be life saving.
Necrotizing Enterocolitis (NE) is the death of intestinal tissue that occurs postnatally in mainly in premature and low birth weight infants (1 in 2,000 - 4,000 births). The underdeveloped gastointestinal tract appears to be susceptible to bacteria, normally found within the tract, to spread widely to other regions where they damage the tract wall and may enter the bloodstream.
- Goldman AS. (2000). Modulation of the gastrointestinal tract of infants by human milk. Interfaces and interactions. An evolutionary perspective. J. Nutr. , 130, 426S-431S. PMID: 10721920
- Fernández L, Langa S, Martín V, Maldonado A, Jiménez E, Martín R & Rodríguez JM. (2013). The human milk microbiota: origin and potential roles in health and disease. Pharmacol. Res. , 69, 1-10. PMID: 22974824 DOI.
- Savino F, Liguori SA, Sorrenti M, Fissore MF & Oggero R. (2011). Breast milk hormones and regulation of glucose homeostasis. Int J Pediatr , 2011, 803985. PMID: 21760816 DOI.
- Lönnerdal B. (2010). Bioactive proteins in human milk: mechanisms of action. J. Pediatr. , 156, S26-30. PMID: 20105661 DOI.
- Manzoni P, Dall'Agnola A, Tomé D, Kaufman DA, Tavella E, Pieretto M, Messina A, De Luca D, Bellaiche M, Mosca A, Piloquet H, Simeoni U, Picaud JC & Del Vecchio A. (2018). Role of Lactoferrin in Neonates and Infants: An Update. Am J Perinatol , 35, 561-565. PMID: 29694997 DOI.
- Cacho NT & Lawrence RM. (2017). Innate Immunity and Breast Milk. Front Immunol , 8, 584. PMID: 28611768 DOI.
- Koyashiki GA, Paoliello MM & Tchounwou PB. (2010). Lead levels in human milk and children's health risk: a systematic review. Rev Environ Health , 25, 243-53. PMID: 21038758
- Gulson BL, Jameson CW, Mahaffey KR, Mizon KJ, Patison N, Law AJ, Korsch MJ & Salter MA. (1998). Relationships of lead in breast milk to lead in blood, urine, and diet of the infant and mother. Environ. Health Perspect. , 106, 667-74. PMID: 9755144
- Ettinger AS, Téllez-Rojo MM, Amarasiriwardena C, Bellinger D, Peterson K, Schwartz J, Hu H & Hernández-Avila M. (2004). Effect of breast milk lead on infant blood lead levels at 1 month of age. Environ. Health Perspect. , 112, 1381-5. PMID: 15471729
- Tanabe S & Kunisue T. (2007). Persistent organic pollutants in human breast milk from Asian countries. Environ. Pollut. , 146, 400-13. PMID: 16949712 DOI.
- LaKind JS, Berlin CM, Sjödin A, Turner W, Wang RY, Needham LL, Paul IM, Stokes JL, Naiman DQ & Patterson DG. (2009). Do human milk concentrations of persistent organic chemicals really decline during lactation? Chemical concentrations during lactation and milk/serum partitioning. Environ. Health Perspect. , 117, 1625-31. PMID: 20019916 DOI.
Van de Perre P. (2003). Transfer of antibody via mother's milk. Vaccine , 21, 3374-6. PMID: 12850343
External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.
- Australia ABC - Diet and nutrition | Healthy Living Pregnancy&Birth
- New Zealand Medsafe - Drug Safety in Lactation | summary of drug distribution into breast milk
- USA American Society for Nutrition
- WHO Breastfeeding
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Cite this page: Hill, M.A. (2018, November 15) Embryology Normal Development - Milk. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Normal_Development_-_Milk
- © Dr Mark Hill 2018, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G